Carcinoma of the breast is now the most common malignant disease of females in the United States. The most critical single factor in determining the success or failure of treatment is the extent of the disease at diagnosis. Early detection programs have uncovered a host of lesions of uncertain prognostic significance upon which a pathological and clinical judgment must be rendered. Diagnosis of these 'borderline' lesions is based primarily upon morphological considerations and is difficult. The development of a method that assists in the pathological distinction of benign and malignant breast lesions would have enormous clinical significance. Loss of normally present blood group antigens ABO(H) on tumors from a variety of organs is associated with the development of invasive or metastatic disease. These findings indicate the need to more fully characterize blood group antigenic changes that occur with neoplastic transformation. A promising new line of inquiry was recently developed based upon the observation that normal human serum contains an antibody against malignant, but not benign (including normal), breast tissues. This antibody, directed against precursor antigens of the human blood group MN system, is termed anti-T (Thomsen) antibody. We have developed a technique for detecting tissue blood group antigens on sections of formalin fixed, paraffin embedded material. Clear immunohistological distinction of benign and malignant breast lesions appears possible by this method, based on the presence of T-antigen on malignant, but not benign or normal epithelium. The present research is undertaken to: 1) determine the effectiveness of this method in discriminating between atypical hyperplastic and malignant breast lesions, 2) define whether expression of blood group antigens on primary breast tumors may be used to predict the development of metastases and, 3) extend these principles to the study of epithelial malignancies other than carcinoma of the breast.